Heart valve disease is the 3rd most prevalent source of cardiovascular disease, leading to ~20,000 deaths per year in the U.S. alone. Moreover, there are an estimated 95,000 valve procedures performed each year in the U.S. and 43% of these are mitral valve (MV) procedures. These numbers will increase substantially in the coming years as our population continues to live longer. Over the next 50 years, the population of Americans age 65+ will more than double - from 34 to 79 million. In fact, the oldest of the old (85+) are currently the fastest growing segment of the population and will more than quadruple by 2050. These numbers are alarming in light of what is known of heart valve disease, particularly in the MV. Today, the 'gold standard' for long-term treatment for MV prolapse, leading to mitral regurgitation (MR), is open-chest repair or replacement surgery, which is highly undesirable for elderly patients. There is a strong clinical need for percutaneous treatment for patients with MMVD as an alternative to open-chest surgery. The goal of this proposal is to develop an imaging strategy for an integrated catheter to reduce the size of enlarged, myxomatous MV leaflets, providing a percutaneous alternative to open-chest surgical leaflet resection. The novelty of this integrated catheter is that it simultaneously uses cryo-anchoring to adhere to a moving MV leaflet, while ablating with radiofrequency (RF) energy to alter the size and intrinsic biomechanical properties of the leaflet tissue. The primary advancements of this proposal will be to successfully guide the catheter and quantify real-time changes of MV geometry and hemodynamics with ultrasound imaging in vivo. First, we will develop the imaging strategy to quantify changes to MV leaflet geometry and hemodynamic function in a swine model (Aim 1). Then, we will demonstrate this strategy's ability to treat myxomatous MV leaflets that lead to MR in a canine model (Aim 2). The endpoint of this research will be demonstration of image-guided delivery of RF energy and validation of reduced MR for the percutaneous treatment of myxomatous MV leaflets. Further, successful completion of each aim will position this strategy for translation into the clinic.